Challenges in developing pMDI technologies

Tick Tock, Watch the Clock!

It is well recognised that a reduction in the development cycle leading to a faster time to market of a drug product reaps both commercial and patient wellbeing benefits. This task becomes even more challenging for a complex combination product such as a pressurised metered dose inhaler (pMDI); in which multi-functional expertise is required in terms of device, drug formulation and manufacturing process development together with appropriate analytical techniques and regulatory affairs management.


Why are pMDI products challenging?

Essentially, because they require a holistic approach which take into consideration the primary packaging components, challenges in formulation and process development all in harmony right at the outset.  However, the traditional approach has been to take a series of steps in isolation whereby a formulation is “fixed” first and then attempts are made to “shoe horn” the device elements to the fixed formulation.  Of course, the development of an aerosol formulation itself is highly complex and needs to take into consideration various factors. When the products contain more than one API – triple therapies are the current trend in asthma/COPD medications – the complexity increases significantly.  Remember that most pMDI products have a shelf life of at least 2 years so up to 200 consistent (i.e. accurate and repeatable) doses have to be delivered over this time in a variety of environmental conditions.



So, what are some of the specific challenges?

In terms of formulations, these would include API morphology, particle sizing, degradation/impurity profiles, electrostatic properties, solubility, potential for crystal growth, and quality/duration of the dispersion. When married with the primary packaging, factors such as moisture ingress, drug deposition, dimensional/physical stability, chemical stability/compatibility, leachables profile and spray characteristics (e.g. velocity, angle and plume geometry) all have to be optimised.

Can we shorten the elements in the product development and approval cycle?

Bespak has developed a theoretical predictive model, which can suggest optimum valve configurations based on a variety of formulation and device component input parameters. This will be showcased at DDL in December 2019 where Ben Thorne, who developed the model, will be available to discuss in greater depth.  It is hoped that this tool will help to shorten valve optimisation lead times. Work is now underway on an additional computational fluid dynamics model to predict ex-actuator spray characteristics, taking into account valve, actuator and formulation properties. At the September 2019 Inhalation and Respiratory Drug Delivery conference in Barcelona, I was interested to note the potential for appropriate in-vitro  techniques to predict in-vivo outcomes and.again, such improved techniques could potentially shorten time to market and also reduce the risk of in-vivo failures.

Are there potential solutions to shorten time to market for complex combination products such as pMDIs?

At Bespak we have established a multi-functional team comprising formulation scientists, material experts, engineers, analysts and regulatory experts to provide a holistic approach to pMDI development.  In addition, we have invested in an array of resources ranging from CT scanners, sophisticated metrology, ‘wet’ chemistry, high speed video spray characterisation equipment, lab scale mixing/filling equipment and the standard range of pMDI characterisation equipment.  We believe we can leverage the human expertise together with the hardware to provide a unique offer to minimise development time and cost.



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